Chronic Active Hepatitis Patients Research Articles

Spontaneous cell-mediated (SCMC) and antibody-dependent cellular cytotoxicity (ADCC) in patients with acute and chronic active hepatitis.

spontaneous (SCMC) and antibody-dependent (ADCC) cellular cytotoxicity was studied in patients with aucte viral hepatitis B and chronic active hepatitis (CAH) B and non-A, non-B. Chang cells displaying the liver-specific protein LSP on the plasma membrane were used as target cells. SCMC and ADCC in acute hepatitis B were not different from normal controls. SCMC and ADCC in chronic active hepatitis B as well as in non-A, non-B were significantly elevated in comparison to normal controls. In additional experiments, the influence of patients sera on SCMC and ADCC was studied. Autologous serum from CAH patients significantly reduced cytotoxicity in SCMC and ADCC assays. This inhibitory capacity of patients sera was attributable to immune complexes, as ultracentrifugation studies and determination of immune complexes of fractionated sera demonstrated.

Serological and tissue markers of HBV infection in chronic active hepatitis patients and in healthy carriers of HBsAg

We studied serological and tissue markers of Hepatitis B virus (HBV) infection in seven healthy carriers of HBsAg and in 58 patients with chronic active hepatitis (CAH), of whom 20 were HBsAg positive and 38 HBsAg negative. Surface antigen was found as the only marker of HBV infection in the liver tissue of all healthy carriers and HBsAg positive in 40% of the CAH patients. Core antigen was detected only in CAH patients: 7/20 HBsAg positive (in two alone and in five together with HBsAg) and 5/38 HBsAg negative (four with circulating anti-HBs and anti-HBc and one with only anti-HBc). All the healthy carriers of the surface antigen presented HBsAg in the liver as the only marker of HBV. Furthermore, all healthy carriers were found to be anti-HBe positive, whereas in the 16 HBsAg positive CAH patients examined for the e system, HBeAg and anti-HBe were found with the same frequency (43.7%). Of the 33 HBsAg negative CAH patients examined, anti-HBe was present in four who also had circulating anti-HBc and anti-HBs. In HBsAg positive CAH patients core antigen was found in the liver tissue of 4/7 HBeAg positive cases and in 2/7 anti-HBe positive, while surface antigen was detected in 3/7 HBeAg positive, 5/7 anti-HBe positive and in the two HBeAg/anti-HBe negative individuals. In HBsAg negative CAH patients, surface antigen was never found in the liver tissue; core antigen was detected, however, in five who had circulating anti-HBc (one in the presence and four in the absence of anti-HBe). In conclusion, from these data it would appear that the various serological patterns of HBV infection, particularly as concerns the presence of antibodies and presence or absence of HBsAg, are not invariably able to predict whether or not HBV antigens are present in liver tissue or, in other words, if active replication does occur.

Viral hepatic diseases and microsomal arylamidase activity in liver tissue.

The relationship between microsomal arylamidase activity, determined by a micromethod, and changes of hepatocytes was studied in biopsy samples taken from 107 patients with normal liver histology and viral hepatic diseases. The activities in healthy carriers and chronic persistent hepatitis patients were significantly greater than those of controls, acute hepatitis and chronic active hepatitis patients, and showed a significant greater than those of controls, acute hepatitis and chronic active hepatitis patients, and showed a significant correlation to morphologic criteria. Ultrastructurally, regularly increased smooth endoplasmic reticulum (SER) was found especially in healthy carriers. The arylamidase activity reflects virus-induced changes of the SER in healthy carriers and viral hepatic diseases.

Intrahepatocytic copper and copper-binding protein in primary biliary cirrhosis. Discrimination from chronic active hepatitis by means of orcein and rubeanic acid techniques.

Liver tissue samples from 111 patients with various hepatic disorders including 37 with primary biliary cirrhosis (PBC) and 22 with chronic active hepatitis (CAH) were studied. Of the PBC patients, 33 out of 37 (89%) showed orcein-positive and rubeanic acid-positive intrahepatocytic copper granules. In the 4 negative cases conventional staining methods revealed characteristic bile duct lesions and granuloma formations; all 4 were so-called presymptomatic patients. Amongst the liver biopsy samples from CAH patients, 12 out of 22 (55%) contained orcein-positive granules, but none showed stainable copper. We conclude that (1) combined orcein and rubeanic acid positivity in liver samples helps to distinguish between PBC and CAH; (2) in presymptomatic PBC the negativity of both methods is adequately compensated by a high frequency of characteristic bile duct lesions and granuloma formation: (3) the absence of orceinophilic intrahepatocytic granules, in our hands, does not accurately predict the response to steroid therapy.

Antigen-specific detection of HBsAg-containing immune-complexes in sera from chronic active hepatitis patients with hepatitis B virus persistent infection by enzyme-immunoassay (EIA).

Clq levels in immune complexes (IC) were determined by a new enzyme-immunoassay (EIA) method to estimate serum antigen-specific HBsAg-containing immune complexes (specific HBsAg-IC). Serum was used from 15 hepatitis patients with persistent hepatitis B virus infection, 2 patients with non-B type chronic active hepatitis (CAH) and 5 healthy persons. This EIA technique detected and assayed HBsAg-IC in patients with hepatitis. Clq levels in specific HBsAg-IC were higher than optical density (OD) 5.00 in 10 of 15 patients, and all 10 patients had CAH and were positive Fc reactive antibody to liver cell membrane. In the other 5 patients Clq levels in specific HBsAg-IC were lower than OD 5.00, and 3 of them had asymptomatic carrier with non-specific reactive hepatitis and 2 had inactive liver cirrhosis.

Different types of smooth muscle antibodies in chronic active hepatitis and primary biliary cirrhosis: their diagnostic and prognostic significance.

The diagnostic and prognostic significance of the different types of serum smooth muscle antibodies (SMA) were investigated in sera of 24 patients with chronic active hepatitis (CAH) and 15 patients with primary biliary cirrhosis (PBC). SMA of IgG class were found in 92% of sera from patients with CAH but in only 20% of sera from PBC patients, whereas the incidence of IgM-SMA was higher in PBC (67%) than in CAH (38%). All six patients with the atypical cholestatic form of CAH has SMA of IgM class, whereas other CAH patients had SMA of mainly IgG class. SMA reacting with rabbit liver (bile canaliculus antibodies, BCA) and with rat glomeruli (glomerulus antibodies) were of anti-actin specificity and were more common in CAH than in PBC. Organ specific BCA or glomerulus antibodies were not found. Anti-actin antibodies were detected in the majority of the investigated sera by an immunoenzymatic anti-actin assay. The results suggest that the determination of SMA titres with heavy chain specific antisera may help in the assessment of diagnosis and prognosis of chronic hepatitis.

Lymphocyte cytotoxicity in human liver disease using rat hepatocyte monolayer cultures

Isolated rat hepatocytes were used to determine the cytotoxicity of peripheral blood mononuclear cells (PBM) from patients with alcoholic liver disease (ALD) and chronic active hepatitis (CAH). The specificity of the cytotoxic effect on liver cells was monitored using rat kidney cells. PBM from patients with CAH and ALD showed increased spontaneous cell-mediated cytolysis (SCMC) for hepatocytes. The SCMC against kidney cells was comparable for the patient groups and controls. Incubation of liver cells with antibody to human liver-specific protein significantly increased the cytotoxic activity of control PBM but did not block cytotoxicity by PBM of patients with CAH. Incubation of PBM from untreated CAH patients with thymosin fraction 5, a polypeptide extract of the thymus gland, significantly lowered cytotoxicity. Our findings suggest that rat liver cells provide a model for studies of cell-mediated immunity in human liver disease and that thymosin fraction 5 decreases the cytotoxic activity of sensitized lymphocytes in CAH.

Humoral Immunoreactivity in Chronic Active Hepatitis: Relation to HLA Antigens

43 patients with chronic active hepatitis (CAH) exhibited significantly higher levels of antibodies against measles and polio type 2 und 3 when compared to 43 age- and sex-matched healthy controls. No significant differences were found for antibodies against polio type 1, rubella, herpes simplex, mumps virus, and tetanus. There was no correlation between antibody levels and the presence of HLA-B8 and/or HLA-B12. The antibody response to vaccination with polio vaccine (killed) and tetanus toxoid was not higher in CAH patients carrying HLA-B8 and/or HLA-B12 than in patients without these antigens. The results indicate that CAH is associated with an increased immunoreactivity, which is, however, not linked to HLA-B8 and/or HLA-B12.

HBsAg-negative chronic active hepatitis related to hepatitis B virus

Numerous cases of chronic hepatitis have been shown to be closely associated with persistent infection with hepatitis B virus (HBV). A group of 100 patients suffering from chronic active hepatitis (CAH) was investigated for HBV serologic markers. Of these, 35 patients were HbsAg-positive; in 26 HBsAg-negative subjects, anti-HBc were detected using counterimmune electrophoresis and complement-fixation tests. These data suggest that chronic liver disease in patients who were only anti-HBc-positive might be related to persistent infection with hepatitis B virus. Epidemiological clinical and histopathological data were different when we compared CAH patients who were HBsAg-negative, but anti-HBc-positive, with HBsAg-positive CAH patients. A sequence is proposed leading from HBsAg-positive to HBsAg-negative CAH, cirrhosis, and hepatoma in temperate areas, according to a model similar to the one described in intertropical Africa.

Hyperviscosity syndrome attributable to hyperglobulinemia in chronic active hepatitis

A young woman with clinical and histological features of chronic active hepatitis was noted to have extremely high levels of immunoglobulin (14.6 g per dl). This was associated with the hyperviscosity syndrome, diffuse coagulation abnormalities, and renal insufficiency in the absence of severe liver disease. Correction of these features occurred with plasmapheresis before corticosteroid therapy was begun. A similar group of persons with very high γ-globulin levels, described previously under the heading of “plasma cell hepatitis,” may form a distinct and rare subgroup of chronic active hepatitis patients.

Alteration in suppressor cell activity in chronic active hepatitis

We have studied peripheral blood mononuclear cells obtained from 24 patients with acute or chronic active hepatitis to determine if there was an abnormality in concanavalin A-induced suppressor cell activity compared to control subjects. Suppressor cells were generated by preincubation of the mononuclear cells with a mitogenic concentration of concanavalin A (6 mug/ml) for 48 hr followed by treatment with mitomycin C and alpha-methyl mannoside. Suppressor cell activity was assessed in second cultures by inhibition of concanavalin A-stimulated blast transformation of fresh allogeneic lymphocytes. Concanavalin A-stimulated suppressor activity was not elicited in mononuclear cells from the majority of patients with chronic active hepatitis in contrast to patients with acute hepatitis or acute inflammatory diseases and controls (P < 0.001). This finding was demonstrable in chronic active hepatitis patients in remission and relapse, both on and off prednisone therapy, and varied considerably during the course of the disease. The extent of liver injury was not related to the measured suppressor cell activity. These studies suggest that in chronic active hepatitis, a disease in which the host immune response may be involved, there appears to be a defect in concanavalin A-stimulated suppressor cells.

Orcein Positive Hepatocellular Material in Long-standing Biliary Diseases

An ultrastructural study of liver cells was performed on 4 patients with primary biliary cirrhosis (PBC) and on 3 patients with chronic active hepatitis (CAH). In liver cells of PBC patients large (ad 2-3 mu in diameter) particles were seen, which morphologically resembed autophagic vacuoles or large secondary lysosymes. The morphology, size, location, and quantity of these particles corresponded to the orcein positive material seen in light microscopy of adjacent sections in specimens from PBC patients. These large particles were not seen in liver cells of CAH patients, which also lacked the orcein positive material in light microscopy. The author suggests that the observed particles indicate the activation of lysosomal compartment in liver cells in PBC, and that the orcein positive material (copper-protein complex accumulating in liver cells in chronic cholestasis) is taken into the phagolysosomal metabolism and processing in liver cells, and possibly resembles in this respect the intracellular metabolism of iron-compounds.

Arthritis Associated with Chronic Active Hepatitis: Complement Activation and Characterization of Circulating Immune Complexes

Circulating immune complexes were identified in cryoproteins isolated from serial serum samples from 6 to 10 patients with chronic active hepatitis (CAH) with frank arthritis and arthralgias. These immune complexes were not detectable in patients with uncomplicated CAH. Only cryoprecipitates from CAH patients with frank arthritis contained IgG, IgM, IgA, and complement components C3, C4, and C5. Hepatitis B surface antigen was concentrated several-fold in the cryoprotein immune complexes as compared with the serum concentration. The C3 activator fragment of the properdin complex was found in fresh serum in all patients with arthritis but was undetectable in patients with arthralagias and uncomplicated CAH. Thus, the presence of circulating complement-fixing immune complexes in patients with alternate complement pathways, and suggests that they play an important role in the pathogenesis of the arthritis.

DISTINCTIONS IN CHRONIC ACTIVE HEPATITIS BASED ON CIRCULATING HEPATITIS-ASSOCIATED ANTIGEN

Thirty cases of chronic active hepatitis in a general hospital population were screened for circulating hepatitis-associated antigen (H.A.A.), antinuclear antibodies (A.N.A.), and the L.E.-cell phenomenon. On the basis of these tests, the patients could be divided into three groups: group I (seven) were positive for H.A.A.; group II (nine) had either A.N.A. or L.E. cells; and group III (fourteen) were negative for all three tests. There was no overlap between groups I and II in that no patient positive for H.A.A. demonstrated antinuclear antibodies or L.E. cells. It was noteworthy that six group-I patients had a history compatible with parenteral transmission of hepatitis virus (shared needles or exposure to blood products) and five had an abrupt rather than insidious onset to their illness. In contrast, group-II patients had no such exposure history, and their illness tended to have an insidious onset. Whether the separation of chronic active hepatitis patients in this manner has significance in regard to course, prognosis, or therapy remains to be determined.